Matches in SemOpenAlex for { <https://semopenalex.org/work/W2792690576> ?p ?o ?g. }
- W2792690576 endingPage "120" @default.
- W2792690576 startingPage "107" @default.
- W2792690576 abstract "Rimonabant is a potent and selective cannabinoid CB1 receptor antagonist widely used in animal and clinical studies. Besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at CB1 receptors. The mechanism underpinning this activity is unclear. Here we show that micromolar concentrations of rimonabant inhibited Gαi/o-type G proteins, resulting in a receptor-independent block of G protein signaling. Accordingly, rimonabant decreased basal and agonist stimulated [35S]GTPγS binding to cortical membranes of CB1- and GABAB-receptor KO mice and Chinese Hamster Ovary (CHO) cell membranes stably transfected with GABAB or D2 dopamine receptors. The structural analog of rimonabant, AM251, decreased basal and baclofen-stimulated GTPγS binding to rat cortical and CHO cell membranes expressing GABAB receptors. Rimonabant prevented G protein-mediated GABAB and D2 dopamine receptor signaling to adenylyl cyclase in Human Embryonic Kidney 293 cells and to G protein-coupled inwardly rectifying K+ channels (GIRK) in midbrain dopamine neurons of CB1 KO mice. Rimonabant suppressed GIRK gating induced by GTPγS in CHO cells transfected with GIRK, consistent with a receptor-independent action. Bioluminescent resonance energy transfer (BRET) measurements in living CHO cells showed that, in presence or absence of co-expressed GABAB receptors, rimonabant stabilized the heterotrimeric Gαi/o-protein complex and prevented conformational rearrangements induced by GABAB receptor activation. Rimonabant failed to inhibit Gαs-mediated signaling, supporting its specificity for Gαi/o-type G proteins. The inhibition of Gαi/o protein provides a new site of rimonabant action that may help to understand its pharmacological and toxicological effects occurring at high concentrations." @default.
- W2792690576 created "2018-03-29" @default.
- W2792690576 creator A5021970002 @default.
- W2792690576 creator A5024422484 @default.
- W2792690576 creator A5031055585 @default.
- W2792690576 creator A5040533199 @default.
- W2792690576 creator A5045189209 @default.
- W2792690576 creator A5050292779 @default.
- W2792690576 creator A5055973742 @default.
- W2792690576 creator A5064774995 @default.
- W2792690576 date "2018-05-01" @default.
- W2792690576 modified "2023-10-12" @default.
- W2792690576 title "Rimonabant, a potent CB1 cannabinoid receptor antagonist, is a Gαi/o protein inhibitor" @default.
- W2792690576 cites W1506141559 @default.
- W2792690576 cites W1515479627 @default.
- W2792690576 cites W1517938530 @default.
- W2792690576 cites W1546852520 @default.
- W2792690576 cites W1579908108 @default.
- W2792690576 cites W1599311640 @default.
- W2792690576 cites W1606957740 @default.
- W2792690576 cites W1654156243 @default.
- W2792690576 cites W179209730 @default.
- W2792690576 cites W1875725323 @default.
- W2792690576 cites W1889694848 @default.
- W2792690576 cites W1931308193 @default.
- W2792690576 cites W1957032487 @default.
- W2792690576 cites W1965926793 @default.
- W2792690576 cites W1971036356 @default.
- W2792690576 cites W1971698096 @default.
- W2792690576 cites W1974740818 @default.
- W2792690576 cites W1975868170 @default.
- W2792690576 cites W1976149002 @default.
- W2792690576 cites W1982291289 @default.
- W2792690576 cites W1985637593 @default.
- W2792690576 cites W1986523501 @default.
- W2792690576 cites W1987669663 @default.
- W2792690576 cites W1991132716 @default.
- W2792690576 cites W1991778481 @default.
- W2792690576 cites W1997161001 @default.
- W2792690576 cites W2000521278 @default.
- W2792690576 cites W2004531640 @default.
- W2792690576 cites W2004802163 @default.
- W2792690576 cites W2005136472 @default.
- W2792690576 cites W2012907914 @default.
- W2792690576 cites W2013387781 @default.
- W2792690576 cites W2015708394 @default.
- W2792690576 cites W2015789312 @default.
- W2792690576 cites W2017316435 @default.
- W2792690576 cites W2021211846 @default.
- W2792690576 cites W2021982247 @default.
- W2792690576 cites W2022305864 @default.
- W2792690576 cites W2030159344 @default.
- W2792690576 cites W2037060024 @default.
- W2792690576 cites W2037680453 @default.
- W2792690576 cites W2038809664 @default.
- W2792690576 cites W2042316523 @default.
- W2792690576 cites W2051377423 @default.
- W2792690576 cites W2059977407 @default.
- W2792690576 cites W2064289262 @default.
- W2792690576 cites W2069105661 @default.
- W2792690576 cites W2070720882 @default.
- W2792690576 cites W2079037043 @default.
- W2792690576 cites W2080727434 @default.
- W2792690576 cites W2090774157 @default.
- W2792690576 cites W2093498450 @default.
- W2792690576 cites W2100554784 @default.
- W2792690576 cites W2102944287 @default.
- W2792690576 cites W2104497132 @default.
- W2792690576 cites W2108443815 @default.
- W2792690576 cites W2119754700 @default.
- W2792690576 cites W2123907272 @default.
- W2792690576 cites W2124517960 @default.
- W2792690576 cites W2127372827 @default.
- W2792690576 cites W2140215853 @default.
- W2792690576 cites W2141229154 @default.
- W2792690576 cites W2148954359 @default.
- W2792690576 cites W2157518435 @default.
- W2792690576 cites W2157658985 @default.
- W2792690576 cites W2165284792 @default.
- W2792690576 cites W2515303181 @default.
- W2792690576 cites W2564621832 @default.
- W2792690576 cites W4211098576 @default.
- W2792690576 cites W4297819556 @default.
- W2792690576 doi "https://doi.org/10.1016/j.neuropharm.2018.01.024" @default.
- W2792690576 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29407764" @default.
- W2792690576 hasPublicationYear "2018" @default.
- W2792690576 type Work @default.
- W2792690576 sameAs 2792690576 @default.
- W2792690576 citedByCount "17" @default.
- W2792690576 countsByYear W27926905762019 @default.
- W2792690576 countsByYear W27926905762020 @default.
- W2792690576 countsByYear W27926905762021 @default.
- W2792690576 countsByYear W27926905762022 @default.
- W2792690576 countsByYear W27926905762023 @default.
- W2792690576 crossrefType "journal-article" @default.
- W2792690576 hasAuthorship W2792690576A5021970002 @default.
- W2792690576 hasAuthorship W2792690576A5024422484 @default.
- W2792690576 hasAuthorship W2792690576A5031055585 @default.